1. Field of the Invention
The present invention relates to compositions based on physiologically acceptable salts of hyaluronic acid, for the treatment and prevention of lesions of the epithelium and of the connective tissue, both human and animal.
Hyaluronic acid is an acid non-sulphurated mucopolysaccharide, being a basic constituent of the connective tissue. In man and animals, hyaluronic acid is present not only in the connective tissue, but also in important biological fluids such as the vitreous humor, the aqueous humor and in the umbilical cord: it has no toxicity and no contraindications for use on man or on animals.
Hyaluronic acid can be obtained by extraction from natural substances, for example from cocks' crests, or can be produced by biotechnology methods. It has a wide molecular weight spectrum which can reach 15,000,000 depending on the method for its production. Hyaluronic acid is known to be used as the sodium or potassium salt in human therapy and in cosmetics: exogenous application of hyaluronic acid has a beneficial effect favoring connective organization and is also effective in reducing or eliminating inflammatory processes induced by germs producing hyaluronase, it facilitates resolution of phlogistic components, reduces excessive capillary permeability, accelerates tissue repair processes and develops an antiedematogenic action by metabolically binding free water to its molecular structures.
Therapeutic indications of hyaluronic acid comprise dermatopathies originating from escoriative abrasions, ulcers deriving from arteriosclerotic vasculopathies, varicose ulcers, cicatrization delays and surgical operations.
In the cosmetics field, hyaluronic acid is used for its invigorating, tonic, skin repair and hydrating properties.
2. Discussion of the Background
U.S. Pat. No. 4,736,024 describes the use of hyaluronic acid and its salts as a vehicle for pharmacologically active substances in pharmaceutical compositions for topical administration.
EP-B-0444492 illustrates the use of hyaluronic acid (and its salts) of high molecular weight (between 800,000 and 4,000,000) for the treatment and prevention of inflammatory states of the oral mucosa.
EP-B-0138572 describes the therapeutic use of fractions of hyaluronic acid and its salts of average molecular weight between 50,000 and 730,000: the fraction (known as “Hyalastine”) of average molecular weight between 50,000 and 100,000 has cicatrizing action on lesions of various kinds; the fraction (known as “Hyalectin”) of average molecular weight between 500,000 and 730,000 is used to treat degenerative and traumatic disturbances of the joints of articulations and to improve their functionality. U.S. Pat. No. 4,517,295 describes a fermentation method for preparing hyaluronic acid and/or its salts (in particular sodium hyaluronate) of high purity, very low viscosity and low molecular weight (including less than 10,000, as stated for example in lines 64-68 of column 4 and lines 6-7 of column 5): this patent specifies that the products obtained in this manner can be used as wetting agents, lubricants, in post-operative use (lines 65-68 of column 1) and for eye pathologies (lines 8-13 of column 5).
U.S. Pat. No. 5,093,487 teaches a method for preparing hyaluronic acid and/or its salts in very pure form, having high molecular weight (up to at least 1,800,000: see lines 47-50 of column 2) and low viscosity (see Example 1 and claims 3 and 14). No specific therapeutic or cosmetic use is indicated.